The Research On Role Of Treg/Th17/Th1Cell And Inflammatory Cytokines In The Development Of Renal Transplant Rejection And Its Clinical Signiifcance

Background: Renal failure is a common clinical disease. In recent years, with thedeepening of the transplantation immunity research and clinical application of newimmunosuppressant, these patients have dramatically improved the prognosis, early survivalrate increased significantly, so the kidney transplant is thought to be an effective method oftreatment of end-stage renal disease, which has attracted much attention, but the occurrence ofpostoperative immune rejection still is a risk factor for effect the long-term graft survival. Sofurther research in kidney transplant recipients body concrete mechanism of graft rejectionand identifying a clinical indicators that can effectively monitor the state of the graft function,which is important clinical significance.Aim: To investigate the levels of circulating regulatory T cells, effector T cells andserum cytokines IL-2, IFN, TNF, IL-4, IL-6, IL-10, IL-17and analyze the associationbetween these laboratory parameters and renal function in renal transplant recipients (RTR),to explore these immune cells and cytokines in the pathogenesis of immune rejection aftertransplantation, to further evaluate its clinical significance.Methods: The numbers of circulating T subsets in renal transplant recipients and healthycontrols was determined by flow cytometry. The concentrations of serum cytokines wasdetermined by cytometric bead array (CBA) and enzyme-linked immunosorbentassay(ELISA). The potential association between the numbers of different subsets of circulating Tcells and cytokines and the values of clinical measures in renal transplant recipients wereanalyzed. The clinical parameters including blood counts, erythrocyte sedimentation rate(ESR), urinary creatinine and urea nitrogen, and estimated glomerular filtration and et al. werecompleted by the trained specialist.Results:1. The number of CD4+CD25-Foxp3+T cells in ESRF patients was significantlygreater than those in HC. In contrast, there was no significant difference in the number ofCD4+CD25+Foxp3+and CD4+CXCR5+Foxp3+T cells in ESRF patients and HC;2. Transplantation resulted in a significant increase in the number of CD4+CD25+Foxp3+and CD4+CXCR5+Foxp3+T cells, as compared to pre-transplant or HC. In contrast, significant decreases were seen in the number of CD4+CD25-Foxp3+T cells followingtransplant in TS patients compared to pre-transplant or HC;3. In ALR or AR patients, the number of CD4+CD25+Foxp3+CD4+CXCR5+Foxp3+T cellsdecreased following transplantation, whereas the number of CD4+CD25-Foxp3+T cellsincreased following transplantation. Moreover, ALR patients displayed greater numbers ofCD4+CD25-Foxp3+T cells and less CD4+CD25+Foxp3+and CD4+CXCR5+Foxp3+T cellsthan AR patients.4. The number of CD4+, CD4+IFN-γ-IL-17+Th17, CD4+IFN-γ+IL-17-Th1andCD4+IFN-γ+IL-17+Th1/17cells in patients with ESRF were significantly greater than the HC.5. In post-transplant TS patients, the number of CD4+, CD4+IFN-γ-IL-17+Th17,CD4+IFN-γ+IL-17-Th1and CD4+IFN-γ+IL-17+Th1/17cells were significantly decreasedcompared to the pre-transplant status.6. Post-transplant RTR patients displayed higher number of CD4+IFN-γ-IL-17+Th17,CD4+IFN-γ+IL-17-Th1and CD4+IFN-γ+IL-17+Th1/17cells compared to the pre-transplantstatus. Moreover, AR patients displayed higher number of CD4+, CD4+IFN-γ-IL-17+Th17,CD4+IFN-γ+IL-17-Th1and CD4+IFN-γ+IL-17+Th1/17cells compared to SAR and CRpatients.7. The concentration of serum IL-2, IFN-γ, TNF-, IL-4, IL-6, IL-10and IL-17in ESRFpatients were significantly increased compared to the HC’s.8. The significantly increased serum levels of IL-2, IFN-γ, TNF-and IL-17inpost-transplant TS’s compared to the pre-transplant patients. TS patients showed an increasedlevel of serum IL-10compared to the pre-transplant RTR’s. However, there was nosignificant difference in the concentrations of IL-4and IL-6pre and post-transplant.9. Post-transplant RTR patients displayed higher levels of serum IL-2, IFN-γ, TNF-andIL-17, but not IL-4and IL-6, compared to the pre-transplant status. Moreover, AR patientsdisplayed higher levels of serum IL-2, IFN-γ, TNF-and IL-17, but not IL-4and IL-6,compared to SAR and CR patients.10. The concentration of serum IL-17and IFN-γ was positively correlated with thenumber of CD4+IFN-γ-IL-17+Th17and CD4+IFN-γ+IL-17-Th1cells, respectively, in the fourgroups. Further analysis of the relationship found a negative association between the numberof CD4+CD25+Foxp3+T cells and the number of CD4+IFN-γ-IL-17+Th17cells in the fourgroups. 11. The numbers of CD4+CD25+Foxp3+and CD4+IFN-γ-IL-17+Th17cells werepositively correlated with the eGFR value and serum creatinine level, respectively, in the fourgroups.. Further analysis revealed that the serum level of TNF-α and IL-17were positivelycorrelated with serum creatinine level. In contrast, the serum level of IL-10was negativelycorrelated with serum creatinine in the four groups..Conclusions:1. These results indicated that the regulatory T cells involved in in thekidney transplant rejection;2. These results indicated that effector T cell and its effect of cytokine secretion (IL-2,IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10and IL-17might be involved in the onset of kidneytransplant rejection process;3. These results indicated that the number of CD4+CD25+Foxp3+T cells were negativelycorrelated with the number of CD4+IFN-γ-IL-17+Th17and CD4+IFN-γ+IL-17-Th1cells cellsin the four groups.4. These results indicated that analysis showed the levels of cytokine-secreting CD4+Tcells was positively correlated with the levels of serum Cr in the four groups, which could beused as clinical indicators for monitoring the course of early stages of renal transplant, toevaluate prognosis and the disease outcome in renal transplant recipients.